Apolipoprotein (apo) A-I has been isolated from a number of subjects with a variant apoA-I isoprotein. The purified apoA-I variant was radioiodinated and injected into normal subjects. The apolipoproteins have been designated as follows: apoA-I-M- from a subject in Milano, Italy; apoA-I-M-2 - from a second unrelated subject in Milano, Italy; apoA-I-T - from a Tangier subject; apoA-I-G - from a subject in Giessen, Germany. The plasma decay of the apoA-I variants was compared to the simultaneous plasma decay of radiolabeled apoA-I-N isolated from normal subjects. Based on the area under the plasma decay curve apoA-I-M, apoA-I-T and apoA-I-G had decreased residence times while the residence times of apoA-I-M-2 was not statistically different when studied in a normal subject. Radiolabelled apoA-I-T decay compared to the decay of apoA-I-N in two subjects with Tangier disease was not different. Radiolabeled apoA-II-T isolated from Tangier subjects, compared to apoA-II-N, isolated from a normal subject, was not statistically different when studied in a normal subject. Radiolabeled apoA-I-N has a decreased residence time when analyzed in a subject with lecithin:cholesterol acryltransferase deficiency, and may contribute to the decreased levels of HDL in patients with this disease. Subjects with type V hyperlipoproteinemia were found to have increased whole body cholesterol synthesis and increased synthesis of plasma triglycerides. Apolipoprotein A-I isoforms, apoA-I-1 and apoA-I-3 were isolated from thoracic duct lymph and plasma respectively. ApoA-I-1, proapoA-I, has a residence time of 4-5 days. Simultaneous metabolic studies with proapoA-I and mature apoA-I revealed a difference of 1 to 2 days in residence times.